2. Academic Validation
  3. A CARM1-targeted therapeutic peptide suppresses breast cancer progression both in vitro and in vivo

A CARM1-targeted therapeutic peptide suppresses breast cancer progression both in vitro and in vivo

  • Pharmacol Res. 2026 Feb:224:108105. doi: 10.1016/j.phrs.2026.108105.
Bing-Ling Peng 1,  Jun Hong 1,  Zi-Rui Wang 1,  Zao-Zao Zheng 1,  Jian-Cheng Ding 1,  Jia-Ying Zhou 1,  Ting Ran 2,  Wen Liu 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
  • 2 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: [email protected].
  • 3 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong 518057, China. Electronic address: [email protected].
PMID: 41548772 DOI: 10.1016/j.phrs.2026.108105
Abstract

Coactivator-associated arginine methyltransferase 1 (CARM1/PRMT4) is well-known for its essential physiological functions and its pivotal role in the development and progression of various cancers. Targeted inhibition of CARM1 activity has emerged as a promising strategy for Cancer treatment. Herein, we report a peptide inhibitor of CARM1 designated as Pi-CARM1, which demonstrates high selectivity for CARM1. The cell-permeable variant, Pi-CARM1 modified with Trans-Activator of Transcription sequence (Pi-CARM1-TAT), effectively inhibits breast Cancer cell proliferation in vitro and significantly reduces tumor growth in mouse models of breast Cancer. Mechanistically, Pi-CARM1-TAT recapitulates the impact of CARM1 on the expression of oncogenic estrogen/ERα-target genes, as well as type I interferon (IFN) and IFN-induced genes (ISGs) in breast Cancer cells. Notably, the combination of Pi-CARM1-TAT with endocrine therapy drugs or etoposide shows synergistic effects in inhibiting breast tumorigenesis. Furthermore, Pi-CARM1-TAT effectively overcomes endocrine therapy resistance in ER-positive breast Cancer cells. In conclusion, we present a novel peptide inhibitor of CARM1, which provides valuable insights and may offer therapeutic potential for the development of CARM1-targeted treatments in breast Cancer.

Keywords

Breast cancer; CARM1; PRMT; Peptide inhibitor.

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